Transfer hydrogenation of ketones with 2-propanol and Raney nickel

Article abstract of DOI:10.1080/00397910701481211

Raney nickel in refluxing 2-propanol containing a trace of HCl is an effective catalytic system for the reduction of ketones to secondary alcohols. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701481211

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Transfer Hydrogenation of Ketones with
2‐Propanol and Raney® Nickel
Robert C. Mebane a , Kimberly L. Holte a & Benjamin H. Gross a
a Department of Chemistry , University of Tennessee at Chattanooga ,
Tennessee, USA
Published online: 14 Aug 2007.
To cite this article: Robert C. Mebane , Kimberly L. Holte & Benjamin H. Gross (2007) Transfer Hydrogenation
of Ketones with 2‐Propanol and Raney® Nickel, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:16, 2787-2791, DOI: 10.1080/00397910701481211
To link to this article: http://dx.doi.org/10.1080/00397910701481211
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Synthetic Communicationsw, 37: 2787–2791, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701481211
Transfer Hydrogenation of Ketones with
2-Propanol and Raneyw Nickel
Robert C. Mebane, Kimberly L. Holte,
and Benjamin H. Gross
Department of Chemistry, University of Tennessee at Chattanooga,
Tennessee, USA
Abstract: Raney nickel in refluxing 2-propanol containing a trace of HCl is an
effective catalytic system for the reduction of ketones to secondary alcohols.
Keywords: ketone reduction, Raney nickel, transfer hydrogenation
We recently reported the efficient reduction of aldehydes to primary alcohols
by transfer hydrogenation using Raney nickel and 2-propanol containing a
trace of hydrochloric acid.[1] The addition of acid was found to accelerate
the transfer reduction by as much as three times. We have now extended this
catalytic system to the reduction of ketones to secondary alcohols, and we
report our results herein. In addition to being an effective method for
reducing ketones, this catalytic combination of Raney nickel and 2-propanol
does not produce metal sludge often encountered in metal hydride reductions[2]
and avoids the need for hydrogen containment as well as the use of pressure
vessels needed in traditional catalytic hydrogenation reactions.[3]
Raney-nickel-catalyzed transfer hydrogenation in refluxing 2-propanol
has been employed by us and others for the reduction of a variety of
compounds including nitriles,[4] iodolactones,[5] aromatic alcohols,[6]
phenols,[7] olefins,[7] aromatic nitro compounds,[8] and certain aromatic
Received in the USA January 10, 2007
Address correspondence to Robert C. Mebane, Department of Chemistry, #2252,
University of Tennessee at Chattanooga, 615 McCallie Ave., Chattanooga, TN
37403-2598, USA. E-mail: robert-mebane@utc.edu
2787

2788
R. C. Mebane, K. L. Holte, and B. H. Gross
Figure 1. Reduction of ketones by catalytic transfer hydrogenation.
hydrocarbons.[9,7] Ketone reduction by this catalytic system has also been
reported.[7,10] However, alcohol yields tended to be low,[10] particularly
when acyclic ketones are used as substrates.[7]
The experimental procedure for the reduction of ketones by catalytic
transfer hydrogenation (CTH) employing Raney nickel and 2-propanol is
simple and straightforward and affords secondary alcohols in good
yields (Fig. 1). In a typical run, the ketone (2 g) is refluxed (condenser
open to the atmosphere) in a magnetically stirred suspension of Raney
nickel (5 g) in 2-propanol (20 mL) containing one drop of concentrated
aqueous HCl. The progress of the reaction is conveniently monitored by
GC-MS. A summary of our results is presented in Table 1. Reaction
products were confirmed by comparison of NMR and mass spectra with
authentic samples. No self-condensation products were detected by GC
or NMR in any of our reactions.
Table 1. Reduction of ketones by catalytic transfer hydrogenation using Raney
nickelw and 2-propanol as the hydrogen source
Yielda Timeb
(%) (min)
Entry
Ketone
2-Octanone
Product(s)
1
2
3
4
5
6
7
8
2-Octanol
96
61
60
82
73
45c
79
91
33
80
17
20
20
40
91
16
5-Methyl-2-hexanone
3-Pentanone
5-Methyl-2-hexanol
3-Pentanol
Cyclohexanol
Cyclohexanone
3-Heptanone
3-Heptanol
Cyclooctanol
3-Octanol
Cyclooctanone
3-Octanone
4-Methylcyclohexanone
cis-4-Methylcyclohexanol (29%)
trans-4-Methylcyclohexanol (71%)
cis-2-Methylcyclohexanol (33%)
trans-2-Methylcyclohexanol (67%)
9
2-Methylcyclohexanone
62
61
10
2-tert-Butylcyclohexanone 2-tert-Butylcyclohexanol
75d 1983
aIsolated yields. Product identities compared to authentic spectra or literature
reference spectra and confirmed by 1H NMR spectroscopy and GC-MS.
bTime to completion determined by GC.
cOnly 45% conversion by GC after 40 min of reflux.
dOnly 75% conversion by GC after 1983 min of reflux.

Transfer Hydrogenation of Ketones
2789
The substrate-to-catalyst ratio (w/w) used to reduce ketones in this study
was approximately 2:5. The Raney nickel catalyst could be used repeatedly (at
least six times) after a simple regeneration step consisting of refluxing the
catalyst in 2-propanol containing KOH (20 mg/1 g of catalyst used) for
15 min, followed by rinsing the catalyst with cold 2-propanol (three times).
As seen in Table 1, cyclic and acyclic ketones are readily reduced to
secondary alcohols by this reductive method. Except for cyclooctanone
(entry 6) and 2-tert-butylcyclohexanone (entry 10), the conversions to
secondary alcohols by CTH were essentially quantitative as determined by
GC (isolated yields are reported in Table 1). As mentioned earlier, in a
previous study employing Raney nickel and 2-propanol, the conversions of
acyclic ketones to secondary alcohols were low.[7] We attribute our
increased conversions to employing a larger catalyst load and to the
inclusion of a trace amount of HCl.
The sluggish reduction of cyclooctanone (entry 6) was somewhat surpris-
ing in light of the fact that cyclohexanone (entry 4) is rapidly reduced. A
careful examination of the minimized structures (MM2) of cyclooctanone
and cyclohexanone reveals the a-equatorial hydrogens in cyclooctanone
may hinder the p-system of the ketone carbonyl from easily interacting
with the catalysis surface. This unfavorable steric interaction of the a-equator-
ial hydrogens is absent in cyclohexanone. The sluggish reduction of 2-tert-
butylcyclohexanone (entry 10) indicates steric bulk around the ketone
carbonyl hinders the reaction.
Reduction of 4-methylcyclohexanone (entry 8) and 2-methylcyclohexa-
none (entry 9) results in a mixture of diastereoisomers with the trans isomer
(equatorial OH) predominating in each case. Interestingly, the cis isomer
(axial OH) has been reported[11] to be the major isomer formed in the
Raney-nickel-catalyzed hydrogenation of 2-methylcyclohexanone using
hydrogen gas and under neutral or basic (NaOH) conditions. (No data
reported for acidic conditions using Raney nickel.) Our results may suggest
that the mechanism by which substrates are reduced by catalytic transfer
hydrogenation and conventional catalytic hydrogenation are not the same
and that the hydrogen donor may play an unique role in the CTH
process.[12] Further work is needed to fully clarify this issue.
The reduction of ketones by CTH does occur without addition the of HCl;
however, the conversions are slower. To illustrate, quantitative conversion of
2-octanone to 2-octanol (entry 1) occurs in just 33 min when trace HCl is
included in the reduction, whereas only 90% conversion of ketone to
alcohol is realized after 378 min when the HCl is excluded. As mentioned
earlier, we observed a similar acceleration by HCl in the reduction of
aldehydes[1] by CTH. Acceleration of traditional catalytic hydrogenations
by acid and using hydrogen gas has also been described,[13] and although
the mechanism of the acceleration is not fully understood, it may result
from an increased interaction between the an activated carbonyl (protonated)
and the catalysis surface.[14]

2790
R. C. Mebane, K. L. Holte, and B. H. Gross
In conclusion, we have demonstrated that secondary alcohols are
conveniently prepared by CTH using Raney nickel and 2-propanol as a
hydrogen donor. Trace HCl accelerates the reductions, and the catalyst can
be used repeatedly after a simple regeneration with KOH in 2-propanol.
EXPERIMENTAL
Raneyw 2800 nickel was obtained from W. R. Grace Company, Chattanooga
Davison. The catalyst was washed prior to use with distilled water (three
times) and 2-propanol (four times). All 1H and 13C NMR spectra were
obtained on a Jeol ECX 400-MHz spectrometer using tetramethylsilane as
internal reference (CDCl3). Mass spectra were recorded on a ThermoElectron
PolarisQ GC-MS. The NMR and mass spectra of the alcohols prepared in this
work were identical to authentic or known spectra.
As an illustrative example of the hydrogenation procedure, 2-octanone
(2.00 g, 15.6 mmol) was added to a mixture of Raney nickel (5 g),
2-propanol (20 mL), and one drop of concentrated aqueous HCl, which had
been refluxed for 5 min. While being magnetically stirred, this reaction
mixture was refluxed for an additional 33 min with the condenser open to
the atmosphere. After cooling to room temperature, the organic layer was
decanted from the Raney nickel, and the catalyst was washed with
2-propanol (3 Â 15 mL). (Raney nickel, is paramagnetic and sticks to the
magnetic stir bar, which facilitates the decantation.) The combined organic
layers were filtered through Celitew, and the 2-propanol was removed by
rotatory evaporation followed by a high vacuum to give 1.95 g (96%) of a
1
colorless liquid whose H and 13C NMR spectra and the mass spectrum
were identical to authentic 2-octanol.
ACKNOWLEDGMENTS
The authors gratefully acknowledge financial support from the Research Cor-
poration, the University of Chattanooga Foundation, and the Grote Chemistry
Fund. In addition, we are indebted to W. R. Grace Company, Chattanooga,
Tennessee, for the generous donation of Raney catalysts.
REFERENCES
1. Mebane, R. C.; Mansfield, A. J. Transfer hydrogenation of aldehydes with
2-propanol and Raney nickel. Synth. Commun. 2005, 35 (24), 3083–3086.
2. Smith, M. B. Organic Synthesis, 2nd Ed.; McGraw-Hill: New York, 2002;
pp. 306–343.

Transfer Hydrogenation of Ketones
2791
3. Vijayalakshmi, P.; Subbarao, R. Hydrogenation of heptaldehyde to heptyl alcohol
with nickel catalysts. J. Am. Oil Chem. Soc. 1993, 70, 435–436.
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